Mini microscope is the new GoPro for studies of brain disease in living mice

March 27, 2019

Working with mice, a team of Johns Hopkins Medicine researchers has developed a relatively inexpensive, portable mini microscope that could improve scientists' ability to image the effects of cancer, stroke, Alzheimer's disease and other conditions in the brains of living and active mice over time. The device, which measures less than 5 cubic centimeters, is docked onto animals' heads and gathers real-time images from the active brains of mice moving naturally around their environments.

"This technology allows us to record really rich amounts of data on the underlying functions of the brain over the lifetime of a disease model," says Arvind Pathak, Ph.D., associate professor of radiology and biomedical engineering at the Johns Hopkins University School of Medicine, and a member of the Johns Hopkins Kimmel Cancer Center.

A report on the development of the mini microscope was published Jan. 9 in Nature Communications.

Traditional microscopes used in brain imaging studies are large stationary microscopes that can be prohibitively expensive and can cost tens of thousands of dollars, say researchers, limiting the number of labs capable of imaging over long periods of time.

Additionally, the bulky nature of benchtop microscopes requires laboratory animals to be completely still for imaging. This often requires animals be repeatedly anesthetized to get clear images. Anesthetized brains undergo changes unrelated to disease, potentially muddying the waters between real results and the brain's response to the anesthetic drug.

The new microscope, which functions like a mini GoPro action camera, is able to capture images in real-time and is fully portable. This eliminates the need to anesthetize animals for imaging, allowing researchers to observe disease changes in a more natural state and relate such changes to the animal's behavior.

In contrast to other mini microscopes, the new microscope offers researchers three imaging options to observe changes in the mouse brain as a disease progresses over time: fluorescence imaging to observe neurons firing or track fluorescently tagged cells; so-called intrinsic optical signal imaging to observe changes in the structure of blood vessels across the course of a disease; and laser speckle contrast imaging to follow changes in blood flow as a disease progresses.

Pathak and his team built the prototype device using commercially available miniature components, such as LED lights, microscope lenses, image sensors and custom-made 3D printed components. The housing, which docks the microscope onto a mouse's head, is entirely 3D printed and reusable. The whole setup, lead author Janaka Senarathna says, then plugs into a laptop computer where researchers can collect and analyze the images.

In a proof-of-concept experiment designed to follow the course of a brain tumor, the research team injected the brains of mice with human brain cancer cells genetically engineered to glow so they can be seen by the microscope. They then mounted the microscope onto the mouse's head, and continuously imaged the mice over 16 days.

In the images gathered during this time, the researchers were able to watch new blood vessels grow alongside the tumor as the cancer progressed. The researchers were then able to measure the blood flow changes during the dynamic remodeling of these blood vessels.

"We successfully monitored these microscopic changes on a daily basis, which allowed us to watch aspects of the disease in remarkable detail," says Pathak.

One remarkable aspect, Pathak said, is that this microscope could be a powerful tool for imaging the effect of new drugs for such diseases.

"This is just one example of the utility of this technology, and one that could someday have an impact on how best to assess response to treatments," says Pathak.

The researchers, who are working with Johns Hopkins Technology Ventures to spin off this technology, say a commercial version might cost approximately 10 times less than currently available models, and they plan to refine the device to capture clearer images and monitor additional brain functions.
-end-
Other researchers involved in this study include, Hang Yu, Callie Deng, Alice Zou, John Issa, Darian Hadjiabadi, Stacy Gil, Qihong Wang, Betty Tyler and Nitish Thakor of the Johns Hopkins University School of Medicine.

This research was supported by the National Cancer Institute (1R21CA175784-01, 1R01CA196701, P30NS050274) and a Kavli neuroscience distinguished fellowship.

Janaka Senarathna, Hang Yu, Nitish Thakor and Arvind Pathak have an international patent (PCT/US18/40979) pending. The remaining authors declare no competing interests.

Johns Hopkins Medicine

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.